Enhanced expression of plasminogen activator inhibitor 1 in patients with nephrotic syndrome

Hypercoagulability is present in patients with nephrotic syndrome. However, alterations in coagulation and fibrinolysis reflected in the glomeruli and urine are not fully understood. We examined plasma and urine concentration s of tissue-type plasminogen activator (tPA) and type 1 plasminogen activat or inhibitor (PAI-1) in 33 patients with nephrotic syndrome (nephrotic grou p). We compared these concentrations with the concentrations in 30 nonnephr otic patients with chronic glomerulonephritis (nonnephrotic group) and with the concentrations in 30 healthy volunteers (control group). We also exami ned fibrin/fibrinogen degradation products in serum and urine and plasma D- dimers, The expression of tPA and PAI-1 was examined in isolated glomeruli using RT-PCR methods. Deposition of fibrinogen/fibrin-related antigen was o bserved by direct immunofluorescence, The incidence of fibrinogen/fibrin-re lated antigen deposition in the nephrotic group was significantly higher th an that in the nonnephrotic group. The concentrations of fibrin/fibrinogen degradation products in serum and urine and of plasma D-dimers were signifi cantly elevated in the nephrotic group as com pared with the nonnephrotic a nd control groups. The plasma concentrations of tPA in the nephrotic group were significantly higher than those in the control group, The urinary excr etion of tPA in the nephrotic group was also significantly higher than in t he nonnephrotic and control groups. The urinary excretion of PAI-1 in the n ephrotic group was higher than that in the control group. The ratio of PAI- 1 mRNA to tPA mRNA in glomeruli was increased in the nephrotic group as com pared with the nonnephrotic group. These results indicate that the fibrinol ytic activity is increased in patients with nephrotic syndrome despite urin ary losses of tPA, However. a relatively enhanced expression of PAI-1 may b e involved in the intraglomerular fibrinogen/fibrin-related antigen deposit ion seen in nephrotic syndrome. Copyright (C) 2001 S. Karger AG, Basel.